G Protein-Coupled Estrogen Receptor Regulates Mesenchymal Stem Cell Mechanotransduction and Differentiation

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction G protein-coupled estrogen receptor (GPER) is a heptahelix estrogen-binding G protein-coupled receptor, and a potential therapeutic target for estrogen-related cancers and diseases. Recently, GPER has been recognized as a key mechano-regulator, but the effects on cell adhesion, spreading, morphology, migration, and differentiation are inconsistent or even contradicting in literature, due to the variations across cell lines and complex crosstalks with ER, and non-genomic actions of other hormones. Here, we focus on investigating the GPER effect on mesenchymal stem cell (MSC) mechanotransduction and differentiation. Methods MSCs treated by synthetic agonist G1 and untreated cells were cultured on fibronectin-coated surfaces. Cell migration was studied by both chemokinesis and chemotaxis experiments. After two-week differentiation, MSC adipogenesis and osteogenesis were evaluated by staining lipid droplets in adipocytes with Oil-Red O and alkaline phosphatase in osteocytes with NBT/BCIP, respectively. In particular, since micropatterns have been widely used to mimic extracellular matrix (ECM) cues, modulate MSC mechanotransduction and differentiation, we investigate the GPER effect on both single-cell and sub-cellular fibronectin microline patterns prepared by microcontact printing. Results GPER activation regulates cytoskeleton organization, with reduced cell polariz

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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